Supporting data for "T cell receptor repertoire sequencing reveals chemotherapy-driven clonal expansion in colorectal liver metastases"

Colorectal liver metastasis (CLM) is a leading cause of colorectal cancer mortality, and the response to immune checkpoint inhibition (ICI) in microsatellite stable CRC has been disappointing. Administration of cytotoxic chemotherapy may cause increased density of tumour infiltrating T cells, which has been associated with improved response to ICI. This study aimed to quantify and characterize T cell infiltration in CLM using T cell receptor (TCR) repertoire sequencing. Eighty-five resected CLM from patients included in the Oslo CoMet study were subjected to TCR repertoire sequencing. Thirty-five and 15 patients had received neoadjuvant chemotherapy (NACT) within a short or long interval, respectively, prior to resection, while 35 patients had not been exposed to NACT. T cell fractions were calculated, repertoire clonality was analysed based on Hill evenness curves, and TCR sequential convergence was assessed using network analysis. <br>Increased T cell fractions (10.6% vs 6.3%) were detected in CLM exposed to NACT within a short interval prior to resection, while modestly increased clonality was observed in NACT exposed tumours independently of the timing of NACT administration and surgery. While private clones made up &gt;90% of detected clones, network connectivity analysis revealed that public clones contributed the majority of TCR sequence convergence. <br>TCR repertoire sequencing can be used to quantify T cell infiltration and clonality in clinical samples. This study provides evidence to support chemotherapy-driven T cell clonal expansion in CLM in a clinical context.

结直肠癌肝转移（Colorectal liver metastasis, CLM）是结直肠癌相关死亡的首要致死原因，而微卫星稳定型结直肠癌（microsatellite stable CRC）对免疫检查点抑制（immune checkpoint inhibition, ICI）治疗的响应效果始终不尽人意。细胞毒性化疗可提升肿瘤浸润T细胞的浸润密度，这与免疫检查点抑制治疗的响应改善密切相关。本研究旨在借助T细胞受体（T cell receptor, TCR）谱型测序技术，对结直肠癌肝转移样本中的T细胞浸润情况进行定量分析与特征解析。本研究纳入奥斯陆CoMet研究中85例经手术切除的结直肠癌肝转移样本，均开展了TCR谱型测序。其中，35例患者在术前短时间窗内接受了新辅助化疗（NACT），15例患者在术前较长时间窗内接受了新辅助化疗，剩余35例患者未接受过新辅助化疗。研究团队计算了样本中的T细胞比例，基于Hill均匀度曲线分析了TCR谱型的克隆性，并通过网络分析评估了TCR序列的趋同性。<br>在术前短时间窗内接受新辅助化疗的结直肠癌肝转移样本中，检测到T细胞比例显著升高（10.6% vs 6.3%）；而无论新辅助化疗与手术的时间间隔如何，接受新辅助化疗的肿瘤样本均呈现出轻度升高的克隆性。尽管私有克隆占检测到的克隆总数的90%以上，但网络连通性分析结果显示，公共克隆贡献了绝大多数的TCR序列趋同事件。<br>TCR谱型测序可用于临床样本中T细胞浸润程度与克隆性的定量分析。本研究为临床背景下化疗驱动结直肠癌肝转移中T细胞克隆扩增提供了实验证据。